Heart failure (HF) and low left ventricular (LV) ejection fraction (EF) are associated with significant risk for stroke and death. However, the value of antithrombotic / antiplatelet therapy to reduce adverse events remains controversial. Warfarin and aspirin are most often used without definitive data. Antiplatelet Trial in Chronic Heart Failure (WATCH) attempted to address this issue, but was prematurely terminated due to poor recruitment. Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) is designed to address this issue. The primary aim of this randomized, double-blind, multi-center clinical trial is to determine whether warfarin (INR 2.5-3.0;target INR 2.75) or aspirin (325 mg per day) is superior for preventing the combined end point of all-cause mortality and stroke (both ischemic and hemorrhagic) in patients with LV EF<35%. The primary null hypothesis is that in patients with EF</=35%, there will be no difference between warfarin and aspirin therapies in time to the first occurrence of death or stroke (ischemic and hemorrhagic). This is tested against the alternative hypothesis of a non-zero difference between these two treatments, at a=.05 two-sided, to detect a 17.82% hazard rate reduction. The top secondary aim is to answer if warfarin or aspirin is superior for reducing combined endpoint of death, stroke, Ml, and HF hospitalization. This trial started in 03/'02. However, study progress was slow and a variety of administrative problems existed. In 06/'05, S. Homma was brought in as a Cardiology PI to oversee the clinical operations. Subsequently, regulatory documents from all sites were brought to compliance and regularly scheduled monitoring visits implemented. Serious adverse events were also adjudicated to assure patient safety. Other changes in organizational structure were implemented to increase data quality. To increase organizational efficiency in the new funding cycle, the grantee institution is planned to be moved to Columbia Univ. (from UMDNJ), where Statistical Analysis Center (J.L.T. Thompson, PI) is also located. Currently, 74 centers in North America, and 66 in Europe are recruiting. At this time, 1,242 patients are enrolled (8/01/'06). Based on the REALISTIC enrollment rate, the total patient number by 08/'11 is expected to be 3,246. Minimum follow up period is 1 year and maximum 6 years. However, given the actual event rates and interruption of therapy rate, the achieved power is likely to be under 80% within the requested funding period. Patients will need be followed for 12 additional months (beyond the end of 5-years) to achieve >80% power. Follow up period will then range from 2 to 6 years. As such, if necessary, we plan to request additional funding after this cycle to obtain appropriate power. With ending of WATCH, this study remains the only study assessing the role of anticoagulation in patients with low EF, with major implications for how the growing number of HF patients will be treated.